This proposal focuses on two principal questions related to virus-host cell interactions: first, how do viruses inhibit the degradation of abnormal proteins in the cells they infect, and second, what are the relationships between cellular proteolytic activities, energy utilization, and effector molecules such as guanosine tetraphosphate (ppGpp). Genetic and biochemical approaches to these questions will be utilized to determine the genes of phages T4 and T7 that function to inhibit abnormal protein degradation in host E. coli cells and the molecular mechanism by which T4 blocks protein degradation. Animal viruses will also be studied to learn whether they block protein breakdown in infected cells. Bacterial mutants that hyperdegrade abnormal proteins have been isolated and characterized as E. coli rho mutants. The Rho protein possesses ATPase and transcription termination activities. The rho mutants show exceptionally low levels of catabolism or normal proteins during periods of starvation; one strain also shows very low levels of ppGpp under these conditions, although RNA synthesis decreases normally. The relationship of ppGpp levels, RNA synthesis and protein degradation will be investigated in other E. coli mutants. In vitro biochemical techniques and genetic methods will be used to ascertain the molecular basis of the altered proteolytic activities in the E. coli mutants. Finally, the mechanism by which certain hyperdegrading E. coli mutants block the production of T4 phages will be investigated.